Oxidative Stress and Redox Signaling in Gastric Cancer: From Mechanisms to Therapeutic Implications.

Oxidative stress, which is characterized by an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, has critical roles in the initiation, progression, and treatment of gastric cancer. On the one hand, an excessive ROS accumulation induces oxidative damage and cancer cell death. On the other hand, moderate levels of ROS cause genetic mutations and dysregulation of signaling pathways to promote proliferation, inflammation, angiogenesis, and metastasis in gastric cancer. Notably, emerging evidence has revealed that ROS also mediate oxidative post-translational modifications (oxPTMs) of redox-sensitive proteins, which can directly affect protein functions and regulate redox signaling in cancer cells. Therefore, elucidating the regulatory mechanisms of oxidative stress and redox signaling in gastric cancer holds great promise to identify novel therapeutic targets or redox-targeting strategies. This review will summarize the mechanisms of oxidative stress in regulating the hallmarks of gastric cancer and highlight the roles of ROS-mediated oxPTMs in gastric cancer. In addition, we will discuss emerging strategies targeting oxidative stress for the treatment of gastric cancer, with an emphasis on the use of bioactive natural products and nanomaterials.